Vasodilatory effect in rat aorta of eriodictyol obtained from Satureja obovata

The vasodilator effect of eriodictyol (5,7,3',4'-tetrahydroxyflavanone), isolated previously from the medicinal plant Satureja obovata Lag., was studied in rat thoracic aorta rings. Eriodictyol relaxed in a concentration-dependent manner the noradrenaline (10(-6) M) and KCl (80 mM) induced contractions. The relaxant effect was more potent in noradrenaline precontracted preparations (IC50 = 6.11 +/- 0.2 x 10(-5) M) than in those precontracted with KCl (IC50 = 2.96 +/- 0.1 x 10(-4) M). Eriodictyol produced weakly concentration-dependent inhibition of the phasic component induced by KCl and noradrenaline while the inhibition of the tonic phase of these contractions was more pronounced. These effects were endothelium independent. In addition, eriodictyol (10(-5) and 5 x 10(-5) M) inhibited CaCl2 cumulative concentration response curves. Eriodictyol weakly inhibited the release of calcium from the sarcoplasmic reticulum and its contribution to the relaxant effect seems to be slight. We have also observed the relaxant effect of eriodictyol on phorbol-12-myristate-13-acetate (PMA) (10(-7) M) induced contractions both in normal calcium (IC50 = 4.69 +/- 0.3 x 10(-5) M) and calcium-free medium (IC50 = 3.74 +/- 0.4 x 10(-5) M). Finally we studied the effects on protein kinase C (PKC) activity. This flavonoid did not show any activity. These results suggest that the vasodilator effect of eriodictyol in rat thoracic aorta could be partially related to the inhibition of calcium influx or other enzymatic protein subsequent to activation of PKC related to the activation of contractile proteins like myosin light chain kinase (MLCK).     

Granulocyte colony-stimulating factor in neutropenic, pediatric solid tumor patients following chemotherapy

Granulocyte colony-stimulating factor (G-CSF) has been used to reduce the duration and/or degree of neutropenia of different etiologies in recent years. In this study, experience with the use of G-CSF (Neupogen, Roche) after 123 courses of highly myelosuppressive chemotherapy administered to 31 (20 female, 11 male) patients with pediatric solid tumors is reported. G-CSF was initialed at a white blood cell (WBC) count of 918 ± 452/μL (100-2000), at a dose of 7.6 ± 2.3 μg/kgl/d (5-14) subcutaneously for 5.2 ± 2.4 days (2-18). G-CSF was given for afebrile neutropenia after 82 and for febrile neutropenia after 41 courses. Only in two episodes where G-CSF was given for afebrile neutropenia, fever developed. The average hospitalization period for febrile neutropenia was 9.8 ± 3.3 days (5-20). Chemotherapy could be given on scheduled time and dosage in 90% of the courses in which G-CSF was used for afebrile neutropenia. G-CSF was well tolerated. Bone pain was observed in two patients and urticaria in one patient. In conclusion, G-CSF increased the WBC count effectively, there were only two febrile episodes in 82 courses in children receiving G-CSF for afebrile neutropenia, it was well tolerated, and it was found to be feasible for use in a developing country.     

Prevalence of self-reported back pain in school children: A study of sociodemographic differences

The study considers the prevalence of back pain experienced in a nationwide random sample of 2173 Icelandic school children aged 11–12 and 15–16. The study found a 20.6% prevalence of at least weekly back pain. The prevalence of back pain was significantly more frequent among the older children. No gender or class difference was found in the overall sample. Older children from rural areas have significantly more back pain than those living in the city. The need for a thorough epidemiological investigation of the association of back pain in children is emphasized.     

Essential and regulatory light chains of Placopecten striated and catch muscle myosins

Summary ATPase activities of molluscan adductor muscle myosins show both muscle and species specific differences: ATPase activity of catch muscle myosin is lower than that of phasic muscle myosin; a 4–5-fold difference exists between the activities of phasic striated muscle myosins from the bay scallop (Argopecten irradians) and sea scallop (Placopecten magellanicus). To characterize the light chains of these myosins we determined the cDNA sequences of the essential light chains and the regulatory light chains from Placopecten striated and catch muscle. The nucleotide sequences of the essential light chains from Placopecten striated and catch muscle myosins are identical and show 94% identity and 98% homology to the Argopecten essential light chain indicating that the tissue and species specific differences in ATPase activities are not due to the essential light chain. We identified three regulatory light chain isoforms, one from striated and two from catch muscle. Sequence differences were restricted to nucleotides encoding some of the N-terminal 52 amino acids. The three recombinant Placopecten regulatory light chain isoforms and the Argopecten regulatory light chain were incorporated into hybrid myosins that contained the essential light chain and heavy chain from Placopecten striated, Placopecten catch, or Argopecten striated muscle. Measurement of the ATPase activities of these hybrids indicates clearly that it is the myosin heavy chain and not the regulatory light chains that are responsible for the muscle and species specific differences in enzymatic activities. Analysis of genomic DNA indicated that these regulatory light chain isoforms are products of a single regulatory light chain gene that is alternatively spliced in the 5 region only.     

Random important alterations in HIV-1 viral quasispecies after antiviral treatment

The evolution of HIV-1 viral populations was studied in a set of MT-2-co-cultured viruses isolated from five patients at the beginning of treatment with zidovudine and after 11-36 months of drug therapy. We first characterized the HIV-1 pol gene to detect the zidovudine-resistance mutations at codons 215 and 219. To analyse the effect that the selective pressure of zidovudine on pol exerted on other genomic regions, we also studied the env gene. The env gene sequence of virus isolated from one individual was unchanged, whereas three other sample pairs had minor alterations in env. In one individual, we detected a significant change in the env gene sequence, and so performed a clonal analysis on viruses isolated before and after treatment. In this individual, the zidovudine-resistant variant that became predominant in the resistant virus population was an undetected minority variant of the viral population before treatment was initiated. These results indicate that the evolution of quasispecies produced by selective pressure on the pol gene from zidovudine treatment could select, in a random process, important changes in other genomic regions; in particular, we describe alterations in the env gene.     

Synaptophysin in spinal anterior horn in aging and ALS: an immunohistological study

Summary Aged-related spinal cord changes such as neuronal loss have been related to the degree of clinical severity of amyotrophic lateral sclerosis (ALS); morphological data on synapses are, however, wanting. Variations in synaptophysin (Sph) expression in aging and ALS were thus studied at the level of lower motor neurons in 40 controls with non-neurological diseases and 11 cases of ALS. Control sections of formalin fixed paraffin embedded cervical (C7/8), thoracic (T10) and lumbar spinal cord (L5) and C6, C7, C8 and L5 of ALS cases were stained with haematoxylin and eosin, luxol fast blue (LFB), and immunostained with a mouse monoclonal antibody against Sph. The neuropil of the anterior horn (AH) in all control cases demonstrated Sph positivity. A dot-like pattern of positivity of presynaptic terminals on soma of motor neurons and fine immunoreactivity along neuronal processes were observed. A significant reduction of Sph immunostaining was observed in the neuropil with increasing age and 3 different somatic patterns were seen: a-well preserved Sph reactivity around the soma and the proximal dendrites of histologically normal neurons; b-few chromatolytic neurons showing large numbers of dot-like presynaptic terminals around the cell body and in a fused pattern; c-intense, diffuse, and homogeneous reactivity of some neurons. Attenuation of Sph reactivity in the AH neuropil, to its complete loss, was observed in all ALS cases. In addition to patterns a-c, two additional microscopic findings were noted in ALS: d-chromatolytic neurons showing complete absence of Sph reactivity; e-absence of Sph reactivity around the soma and the proximal dendrites of histologically normal surviving neurons.Our findings demonstrate that there is a decrease in Sph immunostaining with aging, thus suggesting an alteration in dendritic networks of the AH with aging. Changes in the pattern of Sph immunoreactivity in cell bodies may represent synaptic plasticity and/or degeneration. Reinnervation may also be a possible mechanism as a response to neuronal loss in oldest control cases. Sph reactivity results may thus lend support to the presence of superimposed aging components in ALS cases which may give an insight into explaining the increasing severity of the disease which is encountered with advancing age.